title: Canine X-linked severe combined immunodeficiency. A model for investigating the requirement for the common gamma chain (gamma c) in human lymphocyte development and function.
abstract: Our laboratory has identified and characterized an X-linked severe combined immunodeficiency (XSCID) in dogs that is due to mutations in the common gamma (gamma c) subunit of the interleukin-2 (IL2), IL4, IL7, IL9, and IL15 receptors. Canine XSCID, unlike genetically engineered gamma c-deficient mice, has a clinical and immunologic phenotype virtually identical to human XSCID. It appears that species-specific differences exist in the role of the gamma c and its associated cytokines in mice compared to their role in humans and dogs, suggesting gamma c-deficient dogs may be a more relevant model for studying the role of the gamma c in humans. We are utilizing this model for a variety of studies to address: 1. Fundamental questions concerning the role of the gamma c in cytokine regulation and lymphocyte development. 2. The pathogenesis of XSCID. 3. Strategies for improving bone marrow transplantation outcome. 4. Development and evaluation of strategies for gene therapy. 5. Human hematopoietic stem cell development.
authors.affiliation: Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, USA. felsburg@vet.upen.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Felsburg
authors.forename: R L
authors.initials: RL
authors.lastname: Somberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Hartnett
authors.forename: P S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: S R
authors.initials: SR
authors.lastname: Carding
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004285:Dogs; D008040:Genetic Linkage; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D014960:X Chromosome
chemical_list: D007142:Immunoglobulin gamma-Chains